In order to facilitate the development of the biological and chemical sciences, fluidic microchip technologies are increasingly utilized to perform traditional chemical laboratory functions within a controlled microfabricated environment. Microfabricated chemical instrumentation, also known as “lab-on-a-chip” technology, requires the development of a plurality of microfabricated functional elements or unit processes cooperatively linked on the microchip to perform small volume chemical and biochemical measurements.
These “on-chip” laboratories facilitate the precise transport and analysis of fluidic chemical and biological materials. The known microfluidic devices provide the advantages of reduced analysis time and reagent consumption, ease of automation, and valveless fluid control of nanoliter to sub-nanoliter volumes. A variety of electrically driven separations have been performed within microchannel networks. Microchips have also been developed for controlling chemical reactions, including arrays for solid-phase chemistry, reaction wells for polymerase chain reactions, channels with immobilized enzymes for flow injection analysis, and manifolds for homogenous enzyme assays.
The ability to design and machine channel manifolds with low-volume connections renders microchips suitable for performing several steps of an analytical process on a single device. Microchips that perform multiple chemical reactions with the speed of microscale CE analysis have been fabricated for pre- and post-separation reactions, for DNA restriction digests with fragment sizing, and for cell lysis, multiplex PCR amplification and electrophoretic sizing.
Electrokinetic techniques, i.e., electroosmotically induced fluid transport and/or electrophoretic migration of ions, are the preferred methods of manipulating biological and chemical materials on microfluidic devices. The mixing of two or more liquid-phase materials or the dispensing of a reagent material on a microchip is accomplished by controlling the electric potentials applied to the various reservoirs to electrokinetically drive the materials contained therein through the channels of the microchip. Electrophoresis transports charged species, whereas electroosmosis imparts a velocity to all ions and neutral species. Under conditions where both electroosmosis and electrophoresis are operative, the net velocity of an ion will be the vector sum of the electroosmotic and electrophoretic velocities.
Electrokinetic transport mechanisms are highly effective for effectuating a number of highly useful experiments as identified above. Several applications require the ability to spatially confine a sample material stream with consistent reproducibility. This spatial confinement or “electrokinetic focusing” refers to the use of electrokinetic transport to confine spatially the transport of both fluids and ions. An example of such focusing is disclosed in related U.S. Pat. No. 5,858,187, issued on Jan. 12, 1999, which describes and shows a microfluidic device and method for spatially confining a stream of fluidic material.
Further applications require the ability to dispense a volume segment of a sample material with consistent reproducibility. An example of such dispensing is disclosed in U.S. Pat. No. 5,858,195, granted Jan. 12, 1999, which describes and shows a microfluidic device and method for dispensing a volume segment of a sample material. The entire disclosure of said U.S. Pat. No. 5,858,195 is incorporated herein by reference.
More recently, a need has arisen for an improved microchip wherein the profile of the dispensed segment may be controlled to dispense more minute quantities. Examples of the benefit of shorter axial extent material segments include (i) decreasing the length required for a separation and reducing the analysis time, (ii) enabling faster axial mixing by diffusion of the segment with adjacent materials, and (iii) increasing the number of material segments per unit axial length of channel.